On my desktop, to be read and eventually be discussed, not sooner than tomorrow. Another nice week 
Evolution, Development, Cancer and a little bit of technical problems.
Acquisti C, Poste G, Curtiss D, Kumar S (2007) Nullomers: Really a Matter of Natural Selection?. PLoS ONE 2(10): e1022. doi:10.1371/journal.pone.0001022
Background
Nullomers are short DNA sequences that are absent from the genomes of humans and other species. Assuming that nullomers are the signatures of natural selection against deleterious sequences in humans, the use of nullomers in drug target identification, pesticide development, environmental monitoring, and forensic applications has been envisioned.
Results
Here, we show that the hypermutability of CpG dinucleotides, rather than the natural selection against the nullomer sequences, is likely the reason for the phenomenal event of short sequence motifs becoming nullomers. Furthermore, many reported human nullomers differ by only one nucleotide, which reinforces the role of mutation in the evolution of the constellation of nullomers in populations and species. The known nullomers in chimpanzee, cow, dog, and mouse genomes show patterns that are consistent with those seen in humans.
Conclusions
The role of mutations, instead of selection, in generating nullomers cast doubt on the utility of nullomers in many envisioned applications, because of their dependence on the role of lethal selection on the origin of nullomers.
Frank SA (2007) Maladaptation and the Paradox of Robustness in Evolution. PLoS ONE 2(10): e1021. doi:10.1371/journal.pone.0001021
Background
Organisms use a variety of mechanisms to protect themselves against perturbations. For example, repair mechanisms fix damage, feedback loops keep homeostatic systems at their setpoints, and biochemical filters distinguish signal from noise. Such buffering mechanisms are often discussed in terms of robustness, which may be measured by reduced sensitivity of performance to perturbations.
Methodology/Principal Findings
I use a mathematical model to analyze the evolutionary dynamics of robustness in order to understand aspects of organismal design by natural selection. I focus on two characters: one character performs an adaptive task; the other character buffers the performance of the first character against perturbations. Increased perturbations favor enhanced buffering and robustness, which in turn decreases sensitivity and reduces the intensity of natural selection on the adaptive character. Reduced selective pressure on the adaptive character often leads to a less costly, lower performance trait.
Conclusions/Significance
The paradox of robustness arises from evolutionary dynamics: enhanced robustness causes an evolutionary reduction in the adaptive performance of the target character, leading to a degree of maladaptation compared to what could be achieved by natural selection in the absence of robustness mechanisms. Over evolutionary time, buffering traits may become layered on top of each other, while the underlying adaptive traits become replaced by cheaper, lower performance components. The paradox of robustness has widespread implications for understanding organismal design.
Adamska M, Degnan SM, Green KM, Adamski M, Craigie A, et al. (2007) Wnt and TGF-β Expression in the Sponge Amphimedon queenslandica and the Origin of Metazoan Embryonic Patterning. PLoS ONE 2(10): e1031. doi:10.1371/journal.pone.0001031
Background
The origin of metazoan development and differentiation was contingent upon the evolution of cell adhesion, communication and cooperation mechanisms. While components of many of the major cell signalling pathways have been identified in a range of sponges (phylum Porifera), their roles in development have not been investigated and remain largely unknown. Here, we take the first steps toward reconstructing the developmental signalling systems used in the last common ancestor to living sponges and eumetazoans by studying the expression of genes encoding Wnt and TGF-β signalling ligands during the embryonic development of a sponge.
Methodology/Principal Findings
Using resources generated in the recent sponge Amphimedon queenslandica (Demospongiae) genome project, we have recovered genes encoding Wnt and TGF-β signalling ligands that are critical in patterning metazoan embryos. Both genes are expressed from the earliest stages of Amphimedon embryonic development in highly dynamic patterns. At the time when the Amphimedon embryos begin to display anterior-posterior polarity, Wnt expression becomes localised to the posterior pole and this expression continues until the swimming larva stage. In contrast, TGF-β expression is highest at the anterior pole. As in complex animals, sponge Wnt and TGF-β expression patterns intersect later in development during the patterning of a sub-community of cells that form a simple tissue-like structure, the pigment ring. Throughout development, Wnt and TGF-β are expressed radially along the anterior-posterior axis.
Conclusions/Significance
We infer from the expression of Wnt and TGF-β in Amphimedon that the ancestor that gave rise to sponges, cnidarians and bilaterians had already evolved the capacity to direct the formation of relatively sophisticated body plans, with axes and tissues. The radially symmetrical expression patterns of Wnt and TGF-β along the anterior-posterior axis of sponge embryos and larvae suggest that these signalling pathways contributed to establishing axial polarity in the very first metazoan.
Elser JJ, Kyle MM, Smith MS, Nagy JD (2007) Biological Stoichiometry in Human Cancer. PLoS ONE 2(10): e1028. doi:10.1371/journal.pone.0001028
Background
A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the “Growth Rate Hypothesis”, GRH) proposes that tumors have elevated phosphorus (P) demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation.
Methodology/Principal Findings
We determined the elemental (C, N, P) and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold) in P content (fraction of dry weight) and RNA content and lower in nitrogen (N):P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only ~11% of total tissue P content.
Conclusions/Significance
Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate (“r-selected,” as in colon and lung) while conditions elsewhere may select for reduced mortality rate (“K-selected,” as in liver and kidney).
Little TJ, Nelson L, Hupp T (2007) Adaptive Evolution of a Stress Response Protein. PLoS ONE 2(10): e1003. doi:10.1371/journal.pone.0001003
Background
Some cancers are mediated by an interplay between tissue damage, pathogens and localised innate immune responses, but the mechanisms that underlie these linkages are only beginning to be unravelled.
Methods and Principal Findings
Here we identify a strong signature of adaptive evolution on the DNA sequence of the mammalian stress response gene SEP53, a member of the epidermal differentiation complex fused-gene family known for its role in suppressing cancers. The SEP53 gene appears to have been subject to adaptive evolution of a type that is commonly (though not exclusively) associated with coevolutionary arms races. A similar pattern of molecular evolution was not evident in the p53 cancer-suppressing gene.
Conclusions
Our data thus raises the possibility that SEP53 is a component of the mucosal/epithelial innate immune response engaged in an ongoing interaction with a pathogen. Although the pathogenic stress mediating adaptive evolution of SEP53 is not known, there are a number of well-known candidates, in particular viruses with established links to carcinoma.
Schulz TJ, Glaubitz M, Kuhlow D, Thierbach R, Birringer M, et al. (2007) Variable Expression of Cre Recombinase Transgenes Precludes Reliable Prediction of Tissue-Specific Gene Disruption by Tail-Biopsy Genotyping. PLoS ONE 2(10): e1013. doi:10.1371/journal.pone.0001013
The Cre/loxP-system has become the system of choice for the generation of conditional so-called knockout mouse strains, i.e. the tissue-specific disruption of expression of a certain target gene. We here report the loss of expression of Cre recombinase in a transgenic mouse strain with increasing number of generations. This eventually led to the complete abrogation of gene expression of the inserted Cre cDNA while still being detectable at the genomic level. Conversely, loss of Cre expression caused an incomplete or even complete lack of disruption for the protein under investigation. As Cre expression in the tissue of interest in most cases cannot be addressed in vivo during the course of a study, our findings implicate the possibility that individual tail-biopsy genotypes may not necessarily indicate the presence or absence of gene disruption. This indicates that sustained post hoc analyses in regards to efficacy of disruption for every single study group member may be required.
